The Biochemistry Section has continued to examine the biochemical and pharmacologic factors governing the responsiveness of neoplastic cells to the oncolytic nucleosides: tiazofurin, selenazofurin and arabinosyl-5-azacytidine (araAC). I. Factors governing the responsiveness of tumors to tiazofurin have been studied in the six transplantable lines which formerly constituted the NCI Rodent Tumor Panel, as well as in six cultured human lung cancers at the NCI-Navy. In both series, tumors or cells responsive to tiazofurin accumulated markedly more of the active metabolite TAD (tiazofurin adenine dinucleotide) than their resistant counterparts. Sensitive cells also showed significantly greater depressions in their guanosine nucleotide pools as a consequence of more profound inhibition of IMP dehydrogenase. These experiments warrant the anticipation that measurements of the extent of anabolism of tiazofurin to TAD ought to provide information of prognostic value in clinical trials with this agent. II. Selenazofurin is a new analog of tiazofurin wherein selenium replaces sulfur. Studies have established that the drug is 5 times more potent than tiazofurin in killing cultured P388 cells, and is anabolized to a dinucleotide (SAD) more extensively than tiazofurin. This dinucleotide has now been synthesized chemically and characterized by NMR and mass spectrometry. Kinetically, it is approximately 5 times more potent than TAD with an inhibitory constant of 50 nM. III. AraAC is extensively phosphorylated in native P388 cells, but not at all in a variant, resistant line developed in our laboratory. This resistance has been traced to a deletion of deoxycytidine kinase. The resistant line is cross-resistant to araC and deoxy-5-AC, but not to 5-AC. AraAC is deaminated by renal cytidine deaminase but this enzyme is apparently absent from both the native and variant lines. After anabolism, the drug is also incorporated into nucleic acids: however, in vivo, using tumors of the Rodent Tumor Panel, the extent of such incorporation did not correlate with sensitivity or resistance to araAC.